New treatment combination for advanced left-side colorectal cancer

Inclusion Criteria:

* Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
* Male or female subjects ≥ 18 years, expected lifespan ≥ 12 weeks.
* Patients have histologically or cytologically confirmed RAS and BRAF wild-type, MSS metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
* AJCC/UICC stage IV left-side metastatic colorectal cancer. At least one measurable lesion according to RECIST 1.1.
* The patient has not previously received any systemic treatment specifically targeting advanced or metastatic colorectal cancer, including chemotherapy, monoclonal antibodies such as cetuximab or panitumumab targeting the epidermal growth factor receptor (EGFR), bevacizumab targeting the vascular endothelial growth factor (VEGF), immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 antibodies, and anti-CTLA-4 antibodies. If recurrence or metastasis occurs during or within 6 months after adjuvant or neoadjuvant chemotherapy, adjuvant/neoadjuvant therapy is considered as a first-line systemic treatment for advanced or metastatic disease.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Within 7 days before treatment, the following laboratory test values are obtained and appropriate organ function is present:

Hemoglobin ≥ 90g/L, neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 75 × 10\^9/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (UNL); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × UNL; if there are liver metastases, AST or ALT ≤ 5 × UNL; Serum creatinine ≤ 1.5 × UNL.

* Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 continuous months, are surgically sterile, or are sexually inactive.
* Patients are not allowed to participate in other clinical trials during the study period and willing to comply with the study protocol and visit plan.

Exclusion Criteria:

* Concurrent active malignancy, excluding malignancies with disease-free survival of 5 years or more or in situ carcinoma considered cured after adequate treatment.
* Currently diagnosed with gastrointestinal diseases such as duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions determined by the investigator to potentially cause gastrointestinal bleeding or perforation.
* Experienced thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis, within the 12 months prior to study enrollment.
* Experienced the following conditions within the 12 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class II or above heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure.
* Use of systemic antibiotics for ≥7 days within the 4 weeks prior to study enrollment, or the occurrence of unexplained fever (\>38.5°C) during the screening period/prior to the first dose (fever attributed to the tumor can be considered for enrollment, as determined by the investigator).
* Presence of uncontrolled pleural effusion, ascites, or pericardial effusion within 14 days prior to study enrollment despite appropriate treatment.
* Presence of any unresolved adverse events of Grade 2 or higher (excluding anemia, alopecia, and skin pigmentation) attributed to previous treatments according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
* Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
* Known human immunodeficiency virus (HIV) infection or known active hepatitis (defined as HBV-DNA ≥ 500 IU/ml for hepatitis B, and HCV-RNA above the limit of detection for hepatitis C) or co-infection with hepatitis B and C.
* History of known or suspected allergy to any investigational drug used in the study.
* Pregnancy or lactation in women.
* Pre-menopausal women (last menstrual period \<2 years ago) who do not use or refuse to use effective non-hormonal contraception, or fertile men.
* Presence of other significant physical or mental illnesses or laboratory abnormalities that may increase the risk of participation in the study, interfere with study results, or are deemed unsuitable for participation by the investigator.